Abstract: The invention is based on the finding that endoplasmic reticulum (ER) stress signalling is associated with the pathogenesis of liver disorders such fatty liver, cirrhosis and hepatocellular carcinoma (HCC), and others. The invention identifies novel targets for liver disease therapy which are involved in ER stress signalling, and thereby pertains to compounds and compositions for medical uses, screening approaches to identify therapeutics as well as diagnostic approaches for the identification of disorders or the stratification of certain liver disease patient groups. The invention also pertains to the use of immune checkpoint inhibitors in combination with the compounds or compositions and/or in the treatment of endoplasmic reticulum (ER) stress signalling induced liver cancers.